Colorectal cancer (CRC) ranks among the most prevalent cancers globally, demanding innovative therapeutic strategies. Immunotherapy, a promising avenue, employs cancer vaccines to activate the immune system against tumors. However, conventional approaches fall short of eliciting robust responses within the gastrointestinal (GI) tract, where CRC originates. Harnessing the potential of all-trans retinoic acid (ATRA) and cytosine-phosphorothioate-guanine (CpG), we developed layered nanoparticles using a layer-by-layer assembly method to co-deliver these agents. ATRA, crucial for gut immunity, was efficiently encapsulated alongside CpG within these nanoparticles. Administering these ATRA@CpG-NPs, combined with ovalbumin peptide (OVA), effectively inhibited orthotopic CRC growth in mice. Our approach leveraged the inherent benefits of ATRA and CpG, demonstrating superior efficacy in activating dendritic cells, imprinting T cells with gut-homing receptors, and inhibiting tumor growth. This mucosal adjuvant presents a promising strategy for CRC immunotherapy, showcasing the potential for targeting gut-associated immune responses in combating colorectal malignancies.

中文翻译：

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层层封装全反式视黄酸和 CpG 的纳米颗粒作为靶向结直肠癌的粘膜佐剂

结直肠癌 (CRC) 是全球最常见的癌症之一，需要创新的治疗策略。免疫疗法是一种很有前途的途径，它利用癌症疫苗来激活针对肿瘤的免疫系统。然而，传统方法无法在结直肠癌的起源地胃肠道内引起强烈的反应。利用全反式视黄酸（ATRA）和胞嘧啶硫代磷酸鸟嘌呤（CpG）的潜力，我们使用逐层组装方法开发了层状纳米颗粒来共同递送这些药物。ATRA 对肠道免疫至关重要，它与 CpG 一起被有效封装在这些纳米颗粒内。将这些 ATRA@CpG-NP 与卵清蛋白肽 (OVA) 结合使用，可有效抑制小鼠原位 CRC 生长。我们的方法利用了 ATRA 和 CpG 的固有优势，在激活树突状细胞、用肠道归巢受体印记 T 细胞以及抑制肿瘤生长方面表现出卓越的功效。这种粘膜佐剂为结直肠癌免疫治疗提供了一种有前景的策略，展示了针对肠道相关免疫反应对抗结直肠恶性肿瘤的潜力。